It is a tale of two Pfizers. In 2018 they abandoned research into the leading cause of dementia, Alzheimer’s Disease (AD) (Hawkes 2018). In 2021, they developed the first vaccine for Covid-19 to re...

According to the US National Institute on Aging and the Alzheimer’s Association (NIA-AA), Alzheimer’s disease (AD) should be understood as a biological construct. It can be diagnosed based on AD-characteristic biomarkers only, even if AD biomarkers can be present many years before a person experiences any symptoms of AD. The NIA-AA’s conceptualisation of AD radically challenges past AD conceptualisations. This article offers ananalytic framework for the clarification and analysis of meanings and effects of conceptualisations of diseases such as that of (...) AD. This framework consists of nine questions that allows us to determine how the conceptualisations of diseases, such as that of AD, link or decouple the following terms to/from each other: screening, diagnosis, pathology, disease (along the lines of what have been labelled as “biological-physiological” or “normative” conceptions of disease in philosophy of medicine), symptoms, and illness. It also includes questions regarding how specific decouplings open up for new categories through which people can understand themselves in new ways, and what spaces of possibilities specific conceptualisations (and their decouplings and linkages) open to. The article shows how specific decouplings/linkages can open up not only for the phenomena of pathologisation but also for a distinct, but related phenomenon here termed as diseasisation. (shrink)

Background Biomarker research is gaining increasing attention focusing on the preclinical stages of the disease. Such interest requires special attention for communication and disclosure in clinical contexts. Many countries give dementia a high health policy priority by developing national strategies and by improving guidelines addressing disclosure of a diagnosis; however, risk communication is often neglected. Main text This paper aims to identify the challenges of disclosure in the context of dementia prediction and to find out whether existing clinical guidelines sufficiently (...) address the issues of disclosing a dementia diagnosis and of disclosing the risk of developing dementia in asymptomatic and MCI stage. We will examine clinical guidelines and recommendations of three countries regarding predictive testing and diagnostic disclosure in dementia and Mild Cognitive Impairment to show their potentials and limits. This will provide a background to address ethical implications of predictive information and to identify ways how to proceed further. We will start by examining the guidelines and recommendations by focusing on what there is already and what is missing regarding the challenges of disclosing dementia prediction and MCI. Then, we will highlight the novel ethical issues generated by the shift to identify preclinical stages of the disease by biomarkers. We will argue for the need to develop guidelines for disclosing a risk status, which requires different considerations then disclosing a diagnosis of dementia. Finally, we will make some suggestions on how to address the gap and challenges raised by referring to German Stakeholder Conference, which presents us a good starting point to the applicability of involving stakeholders. Conclusions This paper underlines the need to develop empirically based guidelines that address the ethical and social strategies for risk communication of dementia prediction by genetic as well as non-genetic biomarkers. According to our analysis, the guidelines do not address the new developments sufficiently. International efforts should aim for specific guidelines on counseling, communicating risk and disclosing results. We argue that guidelines on disclosure should be developed by involving various stakeholders and should be informed by socio-empirical studies involving laypersons’ needs and wishes regarding risk communication. (shrink)

An increasing number of people seek medical attention for mild cognitive symptoms at older age, worried that they might develop Alzheimer’s disease. Some clinical practice guidelines suggest offering biomarker testing in such cases, using a brain scan or a lumbar puncture, to improve diagnostic certainty about Alzheimer’s disease and enable an earlier diagnosis. Critics, on the other hand, point out that there is no effective Alzheimer treatment available and argue that biomarker tests lack clinical validity. The debate on the ethical (...) desirability of biomarker testing is currently polarized; advocates and opponents tend to focus on their own line of arguments. In this paper, we show how the method of reflective equilibrium can be used to systematically weigh the relevant arguments on both sides of the debate to decide whether to offer Alzheimer biomarker testing. In the tradition of RE, we reflect upon these arguments in light of their coherence with other argumentative elements, including relevant facts, ethical principles, and theories on societal ideals or relevant concepts, such as autonomy. Our stance in the debate therefore rests upon previously set out in-depth arguments and reflects a wide societal perspective. (shrink)

The Alzheimer field is in desperate need for an effective treatment. After decades of research, the available drugs treat only symptoms, and even their effectiveness is disputed. Because brain changes precede the clinical symptoms by years to decades, disease-modifying treatments should probably be started early, when the first symptoms occur—or even before. But how to determine who to treat? In this issue, Erik Gustavsson c.s. approach this question by addressing the benefits, harms and ethical issues encountered when using different modes (...) of screening for ‘preclinical’ or early symptomatic Alzheimer disease.1 Their overall conclusion is clear—screening for high risk of developing AD dementia to select those who are eligible for treatment is ethically problematic, unless extremely effective treatment becomes available. An additional major challenge is that diagnostic test accuracy is generally poor, with a particularly high risk of false-positive results, that is, biological evidence of Alzheimer pathology in persons who will never develop dementia. The risk of overmedicalisation is serious, and the potential harms of screening for AD should not be ignored, as Le Couteur c.s. previously argued.2 In short, there is no evidence base for any form of screening for AD whether in a preclinical stage (an …. (shrink)

Background Scientific and technological advancements in mapping and understanding the interrelated pathways through which biological and environmental exposures affect disease development create new possibilities for detecting disease risk factors. Early detection of such risk factors may help prevent disease onset or moderate the disease course, thereby decreasing associated disease burden, morbidity, and mortality. However, the ethical implications of screening for disease risk factors are unclear and the current literature provides a fragmented and case-by-case picture. Methods To identify key ethical considerations (...) arising from the early detection of disease risk factors, we performed a systematic scoping review. The Scopus, Embase, and Philosopher’s Index databases were searched for peer-reviewed, academic records, which were included if they were written in English or Dutch and concerned the ethics of (1) early detection of (2) disease risk factors for (3) disease caused by environmental factors or gene-environment interactions. All records were reviewed independently by at least two researchers. Results After screening 2034 titles and abstracts, and 112 full papers, 55 articles were included in the thematic synthesis of the results. We identified eight common ethical themes: (1) Reliability and uncertainty in early detection, (2) autonomy, (3) privacy, (4) beneficence and non-maleficence, (5) downstream burdens on others, (6) responsibility, (7) justice, and (8) medicalization and conceptual disruption. We identified several gaps in the literature, including a relative scarcity of research on ethical considerations associated with environmental preventive health interventions, a dearth of practical suggestions on how to address expressed concerns about overestimating health capacities, and a lack of insights into preventing undue attribution of health responsibility to individuals. Conclusions The ethical concerns arising with the early detection of risk factors are often interrelated and complex. Comprehensive ethical analyses are needed that are better embedded in normative frameworks and also assess and weigh the expected benefits of early risk factor detection. Such research is necessary for developing and implementing responsible and fair preventive health policies. (shrink)

Alzheimer’s Disease (AD) provides an excellent case study to investigate emerging conceptions of health, disease, pre-disease, and risk. Two scientific working groups have recently reconceptualized AD and created a new category of asymptomatic biomarker positive persons, who are either said to have preclinical AD, or to be at risk for AD. This article examines how prominent theories of health and disease would classify this condition: healthy or diseased? Next, the notion of being “at risk”—a state somewhere in-between health and disease—is (...) considered from various angles. It is concluded that medical-scientific developments urge us to let go of dichotomous ways of understanding disease, that the notion of “risk,” conceptualized as an increased chance of getting a symptomatic disease, might be a useful addition to our conceptual framework, and that we should pay more attention to the practical usefulness and implications of the ways in which we draw lines and define concepts. (shrink)

Despite the longstanding debate on definitions of health and disease concepts, and the multitude of accounts that have been developed, no consensus has been reached. This is problematic, as the way we define health and disease has far-reaching practical consequences. In recent contributions it is proposed to view health and disease as practical- and plural concepts. Instead of searching for a general definition, it is proposed to stipulate context-specific definitions. However, it is not clear how this should be realized. In (...) this paper, we review recent contributions to the debate, and examine the importance of context-specific definitions. In particular, we explore the usefulness of analyzing the relation between the practical function of a definition and the context it is deployed in. We demonstrate that the variety of functions that health and disease concepts need to serve makes the formulation of monistic definitions not only problematic but also undesirable. We conclude that the analysis of the practical function in relation to the context is key when formulating context-specific definitions for health and disease. At last, we discuss challenges for the pluralist stance and make recommendations for future research. (shrink)

‘Disease interception’ describes the treatment of a disease in its clinically inapparent phase and is increasingly used in medical literature. However, no precise definition, much less an ethical evaluation, has been developed yet. This article starts with a definition of ‘disease interception’ by distinguishing it from other preventions. It then analyses the ethical and social implications of the concept in light of the four principles of medical ethics by Beauchamp and Childress. The term ‘disease interception’ refers to a form of (...) secondary prevention applied in a short interception window intended to prevent a preclinical disease from developing further. We propose the definition ‘early and targeted secondary prevention by treatment’. The ethical evaluation of the concept shows that while it promises to be beneficial, it raises a number of ethical and social challenges regarding patient autonomy and justice. In order to ensure decision-making that respects patient autonomy, commercially motivated metaphors such as ‘disease interception’ should make way for precise definitions. Future research should not only focus on how to detect clinically inapparent diseases but also on the ethical question, when this is justifiable and what consequences it has for the individual and society as a whole. (shrink)

Epigenetic markers could potentially be used for risk assessment in risk-stratified population-based cancer screening programmes. Whereas current screening programmes generally aim to detect existing cancer, epigenetic markers could be used to provide risk estimates for not-yet-existing cancers. Epigenetic risk-predictive tests may thus allow for new opportunities for risk assessment for developing cancer in the future. Since epigenetic changes are presumed to be modifiable, preventive measures, such as lifestyle modification, could be used to reduce the risk of cancer. Moreover, epigenetic markers (...) might be used to monitor the response to risk-reducing interventions. In this article, we address ethical concerns related to personal responsibility raised by epigenetic risk-predictive tests in cancer population screening. Will individuals increasingly be held responsible for their health, that is, will they be held accountable for bad health outcomes? Will they be blamed or subject to moral sanctions? We will illustrate these ethical concerns by means of a Europe-wide research programme that develops an epigenetic risk-predictive test for female cancers. Subsequently, we investigate when we can hold someone responsible for her actions. We argue that the standard conception of personal responsibility does not provide an appropriate framework to address these concerns. A different, prospective account of responsibility meets part of our concerns, that is, concerns about inequality of opportunities, but does not meet all our concerns about personal responsibility. We argue that even if someone is responsible on grounds of a negative and/or prospective account of responsibility, there may be moral and practical reasons to abstain from moral sanctions. (shrink)